We have recently found that acutely hypophysectomized (HPX) adult mongrel dogs of either sex cannot increase sodium (Na) excretion in response to saline expansion. Oxytocin was the only tested pituitary hormone capable of completely restoring the ability of the saline expanded HPX dog to excrete Na at rates comparable to that of the saline expanded intact adult dog. Furthermore, we have found that serum oxytocin concentrations, determined by radioimmunoassay (RIA), in intact adult dogs increased 5 fold following saline expansion. Newborn dogs (less than three weeks age) also have a limited natriuretic response to saline expansion. We have found that infusion of oxytocin into saline expanded puppies produces significant natriuresis and fractional Na excretion values similar to the saline expanded intact adult. Moreover, serum oxytocin levels in puppies did not increase with saline expansion. We have also found that vagotomy attenuated the response to saline expansion in adult dogs, a condition which could be partially overcome with central vagi stump electrical stimulation. Experiments in adult and newborn dogs are, therefore, designed to determine if: (1) serum oxytocin levels correlate with the degree of volume expansion and resultant Na excretion rates, (2) there is a maturational correlation between serum oxytocin levels and Na excretion, (3) vagotomy reduces the saline expansion-induced oxytocin release and whether these effects can be reversed by electrical stimulation of central vagi stumps, (4) reduced serum oxytocin release accounts for the attenuated natriuresis in caval dogs, (5) the natriuretic effects of oxytocin represent proximal or distal tubular Na inhibition, (6) chronically oxytocin deficient animals (HPX rats) can remain in Na-balance with increases in dietary Na intake, and (7) oxytocin releases a natriuretic mediator substance from the central nervous system.